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Depletion of stearoyl-CoA desaturase(scd)leads to fatty liver disease and defective mating behavior in zebrafish

摘要Stearyl coenzyme A desaturase(SCD),also known as delta-9 desaturase,catalyzes the rate-limiting step in the formation of monounsaturated fatty acids.In mammals,depletion or inhibition of SCD activity generally leads to a decrease in triglycerides and cholesteryl esters.However,the endogenous role of scd in teleost fish remains unknown.Here,we generated a zebrafish scd mutant(scd-/-)to elucidate the role of scd in lipid metabolism and sexual development.Gas chromatography-mass spectrometry(GC-MS)showed that the scd-/-mutants had increased levels of saturated fatty acids C16:0 and C18:0,and decreased levels of monounsaturated fatty acids C16:1 and C18:1.The mutant fish displayed a short stature and an enlarged abdomen during development.Unlike Scd-/-mammals,the scd-/-zebrafish showed significantly increased fat accumulation in the whole body,especially in the liver,leading to hepatic mitochondrial dysfunction and severe cell apoptosis.Mechanistically,srebf1,a gene encoding a transcriptional activator related to adipogenesis,acc1 and acaca,genes involved in fatty acid synthesis,and dgat2,a key gene involved in triglyceride synthesis,were significantly upregulated in mutant livers to activate fatty acid biosynthesis and adipogenesis.The scd-/-males exhibited defective natural mating behavior due to defective genital papillae but possessed functional mature sperm.All defects in the scd-/-mutants could be rescued by ubiquitous transgenic overexpression of scd.In conclusion,our study demonstrates that scd is indispensable for maintaining lipid homeostasis and development of secondary sexual characteristics in zebrafish.

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作者 Shan-Shan Xu [1] Yi Li [2] Hou-Peng Wang [2] Wen-Bo Chen [3] Ya-Qing Wang [2] Zi-Wei Song [3] Hui Liu [3] Shan Zhong [4] Yong-Hua Sun [5] 学术成果认领
作者单位 Department of Genetics,Wuhan University School of Basic Medical Sciences,Wuhan,Hubei 430071,China;State Key Laboratory of Freshwater Ecology and Biotechnology,Hubei Hongshan Laboratory,Institute of Hydrobiology,Innovation Academy for Seed Design(INASEED),Chinese Academy of Sciences,Wuhan,Hubei 430072,China [1] State Key Laboratory of Freshwater Ecology and Biotechnology,Hubei Hongshan Laboratory,Institute of Hydrobiology,Innovation Academy for Seed Design(INASEED),Chinese Academy of Sciences,Wuhan,Hubei 430072,China [2] Department of Genetics,Wuhan University School of Basic Medical Sciences,Wuhan,Hubei 430071,China [3] Department of Genetics,Wuhan University School of Basic Medical Sciences,Wuhan,Hubei 430071,China;Hubei Province Key Laboratory of Allergy and Immunology,Wuhan,Hubei 430071,China [4] State Key Laboratory of Freshwater Ecology and Biotechnology,Hubei Hongshan Laboratory,Institute of Hydrobiology,Innovation Academy for Seed Design(INASEED),Chinese Academy of Sciences,Wuhan,Hubei 430072,China;College of Advanced Agricultural Sciences,University of Chinese Academy of Sciences,Beijing 100049,China [5]
DOI 10.24272/j.issn.2095-8137.2022.167
发布时间 2024-02-23
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动物学研究

动物学研究

2023年44卷1期

63-77页

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